title: Comparisons of metabolic and physiological changes in rats following short term oral dosing with pesticides commonly found in food.
abstract: ¹H Nuclear Magnetic Resonance spectroscopy has been used to profile urinary metabolites in male Fischer F344 rats in order to assess the metabolic changes induced by oral exposure to two benzimidazole fungicides (carbendazim and thiabendazole) and two bipyridyllium herbicides (chlormequat and mepiquat). Exposure levels were selected to be lower than those expected to cause overt signs of toxicity. We then compared the sensitivity of the metabolomics approach to more traditional methods of toxicity assessment such as the measurement of growth and organ weights. Separate, acute exposure experiments were conducted for each pesticide to identify potential metabolic markers of exposure across four doses (and a control). Growth, organ weights and feeding/drinking rates were not significantly affected by any compounds at any dose levels tested. In contrast, metabolic responses were detected within 8 and 24h for chlormequat and mepiquat, and after 24h for carbendazim and thiabendazole. These results demonstrate the potential for the use of metabolomics in food toxicity testing.
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne, VIC 3001, Australia. oliver.jones@rmit.edu.au
authors.forename: Oliver A H
authors.initials: OA
authors.lastname: Jones
authors.forename: Steven
authors.initials: S
authors.lastname: Murfitt
authors.forename: Claus
authors.initials: C
authors.lastname: Svendsen
authors.forename: Anthony
authors.initials: A
authors.lastname: Turk
authors.forename: Hazel
authors.initials: H
authors.lastname: Turk
authors.forename: David J
authors.initials: DJ
authors.lastname: Spurgeon
authors.forename: Lee A
authors.initials: LA
authors.lastname: Walker
authors.forename: Richard F
authors.initials: RF
authors.lastname: Shore
authors.forename: Sara M
authors.initials: SM
authors.lastname: Long
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D015415:Biomarkers / Q000652:urine; D002219:Carbamates / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D002716:Chlormequat / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D006540:Herbicides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D010573:Pesticide Residues / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D010880:Piperidines / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D025341:Principal Component Analysis; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013827:Thiabendazole / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D014116:Toxicology / Q000379:methods*; D006113:United Kingdom
chemical_list: D001562:Benzimidazoles; D015415:Biomarkers; D002219:Carbamates; D005659:Fungicides, Industrial; D006540:Herbicides; D010573:Pesticide Residues; D010880:Piperidines; D002716:Chlormequat; C006698:carbendazim; D013827:Thiabendazole; C049449:mepiquat
keywords: Food safety; Metabolomics; Pesticide; Time course; Toxicology